β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells

• Published in: Biochemical and biophysical research communications 2014-11, Vol.454 (3), p.417-422
• Main Authors: Jeong, Moon Hee, Kim, Jin Hwan, Seo, Kang-sik, Kwak, Tae Hwan, Park, Woo Jin
• Format: Article
• Language: English
• Subjects: DNA, Mitochondrial - genetics; Energy Metabolism - drug effects; Gene Expression Regulation - drug effects; HeLa Cells; Humans; Lactic Acid - metabolism; MELAS; MELAS Syndrome - drug therapy; MELAS Syndrome - genetics; MELAS Syndrome - metabolism; MELAS Syndrome - pathology; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - pathology; NAD - metabolism; Naphthoquinones - pharmacology; NQO1; Reactive Oxygen Species - metabolism; β-Lapachone
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.10.093

•β-Lapachone (β-lap) restored mitochondrial dysfunctions in MELAS cybrid cells.•β-Lap ameliorated the defective energy production and lactic acidosis in MELAS cybrid cells.•β-Lap activated Sirt1 that is known to be a key regulator of mitochondrial biogenesis and metabolism. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD+/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS.